Sulfonamides, antifolates, and fluoroquinolones (Fitz)

Question 1

Sulfonamides are competitive inhibitors of ___

Answer 1

dihydropteroate synthase - an essential enzyme in the folate biosynthesis pathway of many bacteria; no production of dihydropteroate or dihydrofolate

Question 2

This drug is the main sulfonamide in clinical use today and used in fixed dose combos with Trimethoprim

Answer 2

sulfamethoxazole

Question 3

what does trimethoprim inhibit?

Answer 3

dihydrofolate reductase –> no production of tetrahydrofolate

Question 4

list the site of infx and condition associated with H influenza with the use of Trimethoprim-Sulfamethoxazole combo:

Answer 4

H influenza –> resp tract, sinusitis

others include:
-Pneumocystis jiroveci –> lung, pneumonia

Question 5

What are the resistance mechanisms of bacteria against sulfamethoxazole?

Answer 5

• mutation of dihydropteroate synthase

- enhanced acquisition of PABA

Question 6

what are the resistance mechanisms of bacteria against Trimethoprim?

Answer 6

• mutation of DHFR

- overexpression of DHFR

Question 7

What types of pathogens are resistant to trimethoprim-sulfamethoxazole?

Answer 7

Folic acid auxotrophs are naturally resistant (E faecalis)

MRSA is variably susceptible

Question 8

List the main therapeutic uses for sulfamethoxazole/trimethoprim and/or sulfonamides in general:

Answer 8

• uncomplicated UTI
• tx and prevention of Pneumocystis carinii pneumonia (PCP) in HIV pts
• toxoplasmosis in immunosuppressed pts

Question 9

List some adverse effects of sulfonamides:

Answer 9

• hypersensitivity (Stevens-Johnson): occurs with TMP-SMX more than other sulfa drugs
• kernicterus: neonatal encephalopathy, displaces bilirubin from albumin and get poor bilirubin clearance
• hemolytic anemia (attn: pts with X-linked G6PD-deficiency)

Question 10

When is SMX contraindicated in the pregnant/post-pregnant mother?

Answer 10

near term and in breast fed neonate (liver immaturity)

Question 11

In individuals with G6PD deficiency, sulfonamides can cause oxidative stress on erythrocytes. These pts generate insufficient NADPH and an excess of ___

Answer 11

GSSG and H2O2 –> cause Hb denaturation, acute hemolysis, and red cell loss

Question 12

what are adverse effects of trimethoprim?

Answer 12

birth defects d/t folate deficiency, such as CV defects and oral clefts

Careful at the 2-3 month period/1st trimester

Question 13

what is the MOA of fluoroquinolones?

Answer 13

inhibit DNA gyrase (topoisomerase II) and topoisomerase IV

Question 14

Which enzymes are inhibited by fluoroquinolones and what bacteria type are their targets?

Answer 14

inhibition of DNA gyrase is more significant in gram -

inhibition of topoisomerase IV is more significant in gram +

Question 15

how can fluoroquinolone resistance develop?

Answer 15

• mutation of DNA gyrase/topoisomerase
• cell membrane efflux mechanisms
• -decreased number of porins -Multi drug resistance *

Question 16

List the more common 2nd, 3rd, and 4th generation fluoroquinolones:

Answer 16

2nd–> Ciprofloxacin
3rd–> Levofloxacin
4th–> Moxifloxacin

Question 17

What are Gen 2/3/4 fluoroquinolones effective against?

Answer 17

• range of gram - such as H influenza, Moraxela catarrhalis
• Tx of osteomyelitis d/t gram - orgs (fluoroquinolones have high bone penetration)
• Also active against several atypical orgs that cause pneumonia

Question 18

which atypical orgs is ciprofloxacin most effective against? Gram + ?

Answer 18

atypical –> mycoplasma, chlamydia, Mycobacteria, legionella

Gram + –> Bacillus anthracis

Question 19

which atypical orgs is levofloxacin most effective against? Gram + ?

Answer 19

atypical –> More active vs Mycoplasma, chlamydia, legionella

Gram + –> Some gram + cocci, e.g., S pneumoniae

Question 20

which atypical orgs is Moxifloxacin most effective against? Gram + ?

Answer 20

atypical –> More active vs mycoplasma, chlamydia, legionella

Gram + –> enhanced gram + cocci and bacilli, and anaerobes

Has no activity against P aeruginosa

Question 21

Which FQ’s are indicated for community acquired pneumonia?

Answer 21

Ciprofloxacin, levofloxacin, Moxifloxacin, Gemifloxacin

Question 22

Which FQ’s are indicated for acute exacerbation of chronic bronchitis?

Answer 22

levofloxacin, moxifloxacin, gemifloxacin

Question 23

which FQ’s are indicated for acute bacterial rhino sinusitis?

Answer 23

ciprofloxacin, levofloxacin, moxifloxacin

Question 24

which FQ’s are indicated for nosocomial pneumonia?

Answer 24

ciprofloxacin and levofloxacin

Question 25

What are some distinctive uses for ciprofloxacin?

Answer 25

ANTHRAX, osteomyelitis, febrile neutropenia, typhoid fever, abdominal infx

Question 26

what are some distinctive uses for moxifloxacin?

Answer 26

complicated intra-abdominal infx (anaerobic) plus metronidazole

Question 27

what can impair the oral absorption and lower bioavailability of all FQ’s?

Answer 27

antacids
milk, yogurt
vitamin mineral supps with Fe or Zn

take separately, not together

Question 28

What are adverse effects of FQ’s?

Answer 28

CT problems –> Peds warning:cartilage erosion, arthropy; Geriatrics warning: Tendon rupture, tendonitis

Phototoxicity

Prolonged QTc interval –> slows repolarization

Potential risk of peripheral neuropathy taken PO or injection

Question 29

what administered route of FQ’s do not show adverse effects on cartilage development in peds pts?

Answer 29

Topically applied FQ’s –> eye or ear drops

Question 30

This drug combo can be used for opportunistic infx such as toxoplasmosis; pneumocystis jiroveci

Answer 30

Sulfamethoxazole and Trimethoprim

Question 31

what types of pts have higher incidence of adverse effects with the use of sulfa drugs?

Answer 31

AIDS pts (higher doses)

Question 32

What is the drug of choice if you suspect anthrax exposure?

Answer 32

ciprofloxacin

Question 33

what is the drug of choice in an immunocompromised pt who has Pneumocystis jiroveci pneumonia?

Answer 33

Trimethoprim-sulfamethoxazole

Question 34

What is the drug of choice in an HIV-infected pt with a CD4 count of less than 100 uL who has toxoplasmosis?

Answer 34

trimethoprim-sulfamethoxazole